The delta agent is a transmissible hepatitis agent that appears to be defective and requires co-infection with hepatitis B virus for its own synthesis. The agent has a small RNA genome (1 million daltons) that is encapsidated together with delta antigen within a coat of HBs Ag. The agent was discovered in 1977 in Italy, where it is endemic. Evidence for infection with the delta agent is found most frequently in carriers of hepatitis B virus who are repeatedly exposed to blood (hemophiliacs, illicit drug users, etc.). Sensitive assays for delta agent infection have been developed and used to evaluate experimental infection of HBV-carrier chimpanzees. In both man and chimpanzee infection with the delta agent results in very severe hepatitis. The delta agent has been experimentally transmitted to woodchucks chronically infected with the woodchuck hepatitis virus, a hepatitis virus similar to hepatitis B virus. The chimpanzee and woodchuck provide animal model systems for more detailed characterization of this medically important agent. Recently, serologic studies of Yucpa Indians (Venezuela) indicated that delta agent was etiologically associated with severe and often fatal hepatitis in this population which has a high incidence of hepatitis B virus infection. Serologic evidence that the delta agent is associated with severe hepatitis in Brazil (Labrea fever) and Colombia (Santa Marta hepatitis) has also been obtained.